Literacy Skills and Calculated 10-Year Risk of Coronary Heart Disease

Background  

Coronary heart disease (CHD) is a leading cause of morbidity and mortality. Reducing the disease burden requires an understanding of factors associated with the prevention and management of CHD. Literacy skills may be one such factor.     

A Prospective Study of Cutaneous Manifestations of Spinal Dysraphism from India

Abstract: Recognition of cutaneous markers of spinal dysraphism is important to prevent the morbidity associated with underlying spinal anomalies. To investigate the frequency and type of cutaneous stigmata in different forms of spinal dysraphism and to assess the role of ultrasonography and/or magnetic resonance imaging in diagnosing spinal dysraphism at two pediatric dermatology tertiary care centers. Over a 4‐year period, all pediatric patients presenting to the dermatology clinic with dorsal midline cutaneous stigmata were evaluated clinically and with imaging studies (radiography, ultrasonographic examination and magnetic resonance imaging/Doppler). Surgical interventions were planned in conjunction with neurosurgery and orthopedic specialists. On examination, 245 (4.2%) had 285 cutaneous stigmata. Of the 180 patients evaluated with radiography, ultrasonographic examination and magnetic resonance imaging, 50 patients (28%) had spinal dysraphism (with 64 cutaneous stigmata). The most common stigmata associated with occult spinal dysraphism were lipoma (10) and dimples (12) and in open spinal dysraphism lipomeningomyelocoele (10) and meningomyelocoele (10). Statistically, lipomeningomyelocoele/myelomeningocoele, atypical dimples and port‐wine stains were most associated with spinal dysraphism (p < 0.001). In 80 children less than 6 months of age, radiography with ultrasonographic examination revealed an SD in 16, while magnetic resonance imaging was diagnostic in four cases. Ultrasonographic examination performed fairly well in children less than 6 months and in cases of flat cutaneous stigmata it missed only 5% of cases, but in cases with bulky overlying masses (lipoma, hemangioma) it missed 15% of cases.     

Implications of Cytogenetic Abnormalities and Azoospermia Factor Microdeletions in Assisted Procreation

Assisted procreation techniques have revolutionized the management of infertility and have offered hope to millions of infertile couples. The main aim of these proce- dures is to produce healthy offspring. However recent studies on short term outcome of ART have reported a higher incidence of low birth weight, development delay, imprinting defects, sex and autosomal structural abnormalities, major and minor congenital malformation and certain cancers in babies conceived via ART. Further the health of ART conceived children beyond the neonatal period have been less well evaluated. A large number of infertile couples opting for ART have an underlying genetic aetiology. These genetic aberrations are iatrogenitically transmitted via ART. Thus it is important that all couples undergo a detailed and comprehensive genetic evaluation prior to ART.     

Invasive growth associated with cold-inducible RNA-binding protein expression drives recurrence of surgically resected brain metastases

BackgroundSixty percent of surgically resected brain metastases (BrM) recur within 1 year. These recurrences have long been thought to result from the dispersion of cancer cells during surgery. We tested the alternative hypothesis that invasion of cancer cells into the adjacent brain plays a significant role in local recurrence and shortened overall survival.MethodsWe determined the invasion pattern of 164 surgically resected BrM and correlated with local recurrence and overall survival. We performed single-cell RNA sequencing (scRNAseq) of >15,000 cells from BrM and adjacent brain tissue. Validation of targets was performed with a novel cohort of BrM patient-derived xenografts (PDX) and patient tissues.ResultsWe demonstrate that invasion of metastatic cancer cells into the adjacent brain is associated with local recurrence and shortened overall survival. scRNAseq of paired tumor and adjacent brain samples confirmed the existence of invasive cancer cells in the tumor-adjacent brain. Analysis of these cells identified cold-inducible RNA-binding protein (CIRBP) overexpression in invasive cancer cells compared to cancer cells located within the metastases. Applying PDX models that recapitulate the invasion pattern observed in patients, we show that CIRBP is overexpressed in highly invasive BrM and is required for efficient invasive growth in the brain.ConclusionsThese data demonstrate peritumoral invasion as a driver of treatment failure in BrM that is functionally mediated by CIRBP. These findings improve our understanding of the biology underlying postoperative treatment failure and lay the groundwork for rational clinical trial development based upon invasion pattern in surgically resected BrM.     

SCN1A‐related phenotypes: Epilepsy and beyond

SCN1A, encoding the alpha 1 subunit of the sodium channel, is associated with several epilepsy syndromes and a range of other diseases. SCN1A represents the archetypal channelopathy associated with a wide phenotypic spectrum of epilepsies ranging from genetic epilepsy with febrile seizures plus (GEFS+), to developmental and epileptic encephalopathies (DEEs). SCN1A disorders also result in other diseases such as hemiplegic migraine and autism spectrum disorder (ASD). Dravet syndrome (DS) is the prototypic DEE with an early onset of febrile status epilepticus, hemiclonic or generalized tonic‐clonic seizures, and later onset of additional seizure types. Electroencephalography (EEG) and magnetic resonance imaging (MRI) are normal at onset. Development is normal in the first year of life but plateaus rapidly, with most patients ultimately having intellectual disability. Epilepsy is drug‐resistant and necessitates polytherapy. Most pathogenic variants occur de novo in the affected child, but they are inherited from mosaic affected or unaffected parents in rare cases. The molecular finding of haploinsufficiency is consistent with a loss‐of‐function defect in cells and animal models. Although seizures are the most commonly reported symptom in DS, many additional issues critically affect patients’ cognitive and behavioral functioning. Hemiplegic migraine (HM) is a rare form of migraine with aura, characterized by the emergence of hemiparesis as part of the aura phase. All SCN1A mutations reported in sporadic/familial HM3 are missense mutations. Most of the experimental results show that they cause a gain of function of Na_V1.1 as opposed to the loss of function of the epileptogenic Na_V1.1 mutations. SCN1A and SCN2A pathogenic variants have been identified in genetic studies of cohorts of patients with ASD. In addition, ASD features are often reported in patients with Dravet syndrome and other DEEs.     

Similarities and differences between primary and secondary degeneration of the optic nerve and the effect of minocycline

Purpose

To investigate the mechanism of secondary degeneration of the optic nerve, and to evaluate the neuroprotective effect of minocycline in this process.

Methods

A partial transection model that morphologically separates primary and secondary degeneration was applied unilaterally in 152 Wistar rat eyes. The involvement of pro-apoptotic, pro-survival and inflammatory pathways was analyzed by quantitative real-time PCR and immunohistochemistry at multiple time points. The neuroprotective effect of daily intraperitoneal injections of minocycline 22?mg/kg/day was evaluated at 7, 11 and 21?days post-injury. Retrograde labeling of retinal ganglion cells (RGCs) with fluorogold was via the superior colliculus, and surviving RGCs were counted using retinal whole mounts.

Results

Both primary and secondary degeneration led to a significant up-regulation of the pro-apoptotic genes, GADD45??, ei24 and CDK2, and the pro-survival gene, IAP-1. These processes differed, however, in their reaction to minocycline. Minocycline protected RGC death from secondary degeneration at 11?days (6?±?8% loss compared to 37?±?7% in the saline-treated group, n?=?15, P?=?0.012), and at 21?days (42?±?7% versus 64?±?7% respectively, n?=?15, P?=?0.06) after partial transection. In contrast, its effect on primary degeneration was not significant.

Conclusions

While the genetic profile supported similarities between primary and secondary degeneration of the optic nerve, the specific effect of minocycline on secondary degeneration revealed a potential difference between the two. The mechanism underlying secondary degeneration, and its role in optic neuropathies such as glaucoma, awaits further studies.